The group III mGlu receptor agonist ACPT-I exerts anxiolytic-like but not antidepressant-like effects, mediated by the serotonergic and GABA-ergic systems

• Published in: Neuropharmacology 2009-09, Vol.57 (3), p.227-234
• Main Authors: Stachowicz, K., Kłodzińska, A., Palucha-Poniewiera, A., Schann, S., Neuville, P., Pilc, A.
• Format: Article
• Language: English
• Subjects: ACPT-I; Animals; Anti-Anxiety Agents - administration & dosage; Anti-Anxiety Agents - pharmacology; Antidepressive Agents - administration & dosage; Antidepressive Agents - pharmacology; Anxiety; Anxiety - drug therapy; Cyclopentanes - administration & dosage; Cyclopentanes - pharmacology; Depression; Depression - drug therapy; Diazepam; Elevated plus-maze test; Flumazenil - pharmacology; Forced swim test; GABA; GABA-A Receptor Antagonists; gamma-Aminobutyric Acid - metabolism; Group mGlu III receptors; Imipramine; Injections, Intraperitoneal; Male; mGlu4 receptors; mGlu8 receptors; Mice; Piperazines - pharmacology; Pyridines - pharmacology; Rats; Rats, Wistar; Receptors, Metabotropic Glutamate - agonists; Ritanserin - pharmacology; Serotonin; Serotonin - metabolism; Serotonin 5-HT1 Receptor Antagonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists - pharmacology; Stress, Psychological - complications; Stress, Psychological - drug therapy; Stress-induced hyperthermia; Tail suspension test; Tricarboxylic Acids - administration & dosage; Tricarboxylic Acids - pharmacology; Vogel test
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2009.06.005

Our earlier studies have demonstrated that (1 S,3 R,4 S)-1-aminocyclo-pentane-1,3,4-tricarboxylic acid ACPT-I, a group III mGlu receptor agonist, produced anxiolytic-like and antidepressant-like actions after central administration. Here we describe the anxiolytic-like effects of ACPT-I after intraperitoneal administration in the stress-induced hyperthermia (SIH), elevated plus-maze (PMT) tests in mice and in the Vogel test in rats. However, the compound did not produce antidepressant-like effects in the tail suspension test (TST) or in the forced swim test (FST) in mice. The potential anxiolytic effect of ACPT-I (20 mg/kg) in the SIH test was inhibited by the benzodiazepine receptor antagonist flumazenil (given i.p., 10 mg/kg), and by a 5-HT 1A receptor antagonist N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}- N-(2-pyridynyl) cyclohexane-carboxamide (WAY100635) (0.1 mg/kg s.c.). At the same time, ritanserin (0.5 mg/kg i.p.), the 5-HT2A/C receptor antagonist, did not change the anxiolytic-like effects of ACPT-I. The results of these studies indicate that the GABA-ergic and serotonergic systems are involved in the potential anxiolytic action of ACPT-I.